Bone Metabolism and Body Composition in Young Athletes

年轻运动员的骨代谢和身体成分

• 批准号: 8600710
• 负责人: Madhusmita Misra
• 金额: $ 18.6万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8600710
• 关键词: Adipose tissue; Adolescence; Adolescent; Adolescent and Young Adult; Adult; Affect; Amenorrhea; Award; Body Composition; Body fat; Bone Density; Clinical; Complex; Contraceptive Agents; Deterioration; Development; Distal; Dual-Energy X-Ray Absorptiometry; Educational process of instructing; Endocrinology; Ensure; Environment; Estradiol; Estrogens; Ethics; Fatty acid glycerol esters; Finite Element Analysis; Funding; Funding Opportunities; Goals; Gonadotropins; Grant; Habits; Hormones; Hypogonadism; Impairment; Institution; Insulin-Like Growth Factor I; Leptin; Longitudinal Studies; Marrow; Measures; Mentors; Metabolic; Midcareer Investigator Award in Patient-Oriented Research; Oral; Pattern; Physiological; Population; Protocols documentation; Radial; Randomized; Randomized Controlled Trials; Reporting; Research; Research Personnel; Research Support; Resources; Risk; Structure; Techniques; Testing; Thick; Time; Training; Training Programs; Visceral; Weight; Woman; Work; adipokines; adiponectin; base; bone; bone health; bone mass; bone metabolism; bone strength; career; design; ghrelin; innovation; interest; multidisciplinary; novel; patient oriented; patient oriented research; pill; programs; prospective; public health relevance; sedentary; subcutaneous; substantia spongiosa; success; therapeutic development; tibia; transdermal estrogen; treatment strategy; young adult

DESCRIPTION (provided by applicant): Mentoring is a critical component of the career of a patient-oriented-researcher, and essential for a successful career in patient-oriented research. The PI has a successful record of mentoring a number of fellows and trainees in the complex techniques of metabolic and bone health assessment in a large population of young athletes, particularly those with associated amenorrhea. The scientific aims of the application are based on the candidate's successfully funded R01, investigating: 1) whether low fat mass and altered levels of adipokines and fat regulated hormones determine alterations in LH pulsatility patterns in amenorrheic athletes (AA), that differentiate them from eumenorrheic athletes (EA) and non-athletes, and 2) treatment strategies to optimize bone accrual and structure in AA over a 12-month period. Several new directions are proposed in the current application, and it is hypothesized (1) that bone strength [assessed using finite element analysis (FEA)] is lower in AA compared with EA and non-athletes 14-21 y at baseline and decreases prospectively over a one- year duration in AA, whereas bone strength increases in EA over the same duration, (2) that greater visceral adipose tissue (VAT) and marrow fat are associated with lower bone density, impaired microarchitecture and lower bone strength, and (3) that in young AA, compared to oral estradiol or no treatment, transdermal estradiol replacement will increase bone strength to approximate that in controls, associated with decreases in marrow fat and no changes in regional body composition. Detailed assessment of regional body composition and bone strength will be performed. Adipocytokines will be measured and related to changes in bone density, structure and strength in longitudinal studies, controlling for traditional risk factrs. The mentoring goals of this proposal include the development of a comprehensive multidisciplinary mentoring and training program, in which trainees will be selected, based on their interest in patient oriented research, work habits and ethical standards. Projects will be selected that are unique and achievable, and significant time will spent by the PI guiding trainees in protocol design, regulatory requirements, didactic coursework, and funding opportunities. Trainees will be exposed to detailed techniques of body composition and bone strength assessment. This K-24 proposal is critical to support the PI's significant time spent in mentoring. The training environment at the PI's institution is outstanding in terms of didactic resources and availability of techniques to assess complex metabolic endpoints. Importantly, the PI enjoys significant support from her Unit and Division Chiefs, who have enthusiastically endorsed her successful mentoring efforts to date and the plans in the current proposal. Taken together, the proposed K-24 application offers a strong mentoring program in patient oriented research that is based on the teaching of important principles of endocrinology and metabolism. The studies are to be carried out in a population at significant risk for impaired bone accrual, with which the PI has significant expertise. The Midcareer Investigator Award in Patient Oriented Research is an ideal mechanism to ensure the necessary support to reduce clinical and administrative responsibilities, and ensure the candidate's continued success as a mentor and clinical researcher.

描述（由申请人提供）：指导是以患者为导向的研究人员职业生涯的重要组成部分，对于以患者为导向的研究取得成功的职业生涯至关重要。 PI 拥有在大量年轻运动员（尤其是闭经相关运动员）的代谢和骨骼健康评估复杂技术方面指导许多研究员和学员的成功记录。该申请的科学目标基于候选人成功资助的 R01，研究：1) 低脂肪量以及脂肪因子和脂肪调节激素水平的改变是否决定闭经运动员 (AA) 的 LH 搏动模式的改变，从而将其与正常经经的运动员区分开来运动员 (EA) 和非运动员，以及 2) 在 12 个月内优化 AA 骨增长和结构的治疗策略。当前的申请中提出了几个新的方向，并假设 (1) 与 EA 和非运动员相比，14-21 岁时 AA 的骨强度 [使用有限元分析 (FEA) 评估] 较低，并且会预期下降AA 的骨强度在一年内增加，而 EA 的骨强度在相同的时间内增加，(2) 较大的内脏脂肪组织 (VAT) 和骨髓脂肪与较低的骨密度、受损的骨密度相关。 (3) 在年轻的 AA 中，与口服雌二醇或不治疗相比，透皮雌二醇替代会增加骨强度，接近对照组，与骨髓脂肪减少相关，且局部身体成分没有变化。将进行区域身体成分和骨强度的详细评估。在纵向研究中，将测量脂肪细胞因子并将其与骨密度、结构和强度的变化联系起来，控制传统的风险因素。该提案的指导目标包括制定全面的多学科指导和培训计划，其中将根据学员对以患者为导向的研究的兴趣、工作习惯和道德标准来选择学员。将选择独特且可实现的项目，PI 将花费大量时间指导学员进行方案设计、监管要求、教学课程和融资机会。学员将接触到身体成分和骨强度评估的详细技术。这份 K-24 提案对于支持 PI 投入大量时间进行指导至关重要。 PI 机构的培训环境在教学资源和评估复杂代谢终点的技术可用性方面非常出色。重要的是，PI 得到了她的单位和部门负责人的大力支持，他们热情地认可了她迄今为止成功的指导工作以及当前提案中的计划。总而言之，拟议的 K-24 应用程序为以患者为导向的研究提供了强有力的指导计划，该计划基于内分泌学和新陈代谢的重要原理的教学。这些研究将在骨生成受损的显着风险人群中进行，PI 拥有丰富的专业知识。以患者为导向的研究中的职业生涯中期研究员奖是一种理想的机制，可确保提供必要的支持，减少临床和行政责任，并确保候选人作为导师和临床研究人员持续取得成功。